CWRU receives NCI grant to advance treatment of gastrointestinal cancers

Case Western Reserve UniversitySep 19 2011

The National Cancer Institute has awarded $11.3 million to Case Western Reserve University School of Medicine to establish a center of excellence for research on gastrointestinal cancers. The funding designates the university as a Specialized Program of Research Excellence (SPORE) in Gastrointestinal (GI) Cancers - recognition extended to just one institution this year. University Hospitals Case Medical Center is the primary affiliate of Case Western Reserve and is collaborating with the School of Medicine on a portion of the comprehensive program.

"This grant reflects the culmination of decades of remarkable research efforts that have advanced our understanding of some of the most devastating and challenging forms of cancer," Case Western Reserve President Barbara R. Snyder said. "We are proud of that progress and profoundly hopeful for future breakthroughs."

This award recognizes extraordinary achievements and potential of the School of Medicine's programs in gastrointestinal malignancies. Case Western Reserve will join an elite group of six other institutions nationwide that hold a SPORE in gastrointestinal cancers. Others include Harvard and Johns Hopkins University. The new funding will be used to build on Case Western Reserve researchers' existing discoveries and push them forward to provide more effective modes of detection, treatment and prevention for patients.

The Case Western Reserve SPORE will focus on translational research aimed at reducing the incidence and deaths from colon cancers and from cancers of the esophagus The SPORE will also develop new approaches for treatment and prevention of adenomatous colon polyps that can develop into colon cancers, and for Barrett's esophagus, that can develop into esophageal cancer. Colon cancer is the second-leading cause of cancer death in the United States, and cancers of the esophagus are (along with melanomas) the most rapidly increasing cause of cancer deaths in the United States.

"We believe passionately in the importance of bench-to-bedside research - that is, to ensure discoveries made in laboratories effectively reach the patients who need them most," said Pamela B. Davis, MD, PhD, Dean of the School of Medicine and Vice President for Medical Affairs, Case Western Reserve University. "This award aligns directly with that approach, and the work it funds ultimately will change lives."

The SPORE studies will develop new tests to identify persons susceptible to GI cancers; new methods to prevent these cancers; new treatments for these cancers; and clinical trials to apply these advances directly to patients.

SPORE studies will benefit the large population of individuals that are affected by GI cancers. They will also work with high risk groups that may not be screened for colon cancers, to develop easy-to-access screening tests. This will include African-Americans, a population highly vulnerable to colon cancer. Since early detection saves lives, this advance will have significant impact on individuals most at risk.

The SPORE will be directed by Dr. Sanford Markowitz, the Dr. Sanford Markowitz/Frances Wragg Ingalls Professor of Cancer Genetics at Case Western Reserve University School of Medicine and a medical oncologist at University Hospitals Seidman Cancer Center. The SPORE is co-directed by Dr. Nathan Berger, the Hanna-Payne Professor of Experimental Medicine at Case Western Reserve School of Medicine, and a hematologist-oncologist at the Seidman Cancer Center. Drs. Markowitz and Berger will lead the SPORE team of 15 doctors and scientists, 11 from the School of Medicine, and its principal affiliate, University Hospitals Case Medical Center, and three from Cleveland Clinic. The Cleveland team is also joined by Dr. James K. V. Willson, Director of Simmons Cancer Center at the University of Texas Southwestern Medical Center, and by Dr. Willson's Dallas-based team of investigators.

"I am honored to lead the outstanding team of physicians and scientists who have joined in the SPORE," said Dr. Markowitz. "Our SPORE trials will be conducted here in Cleveland, and members of our community will be among the first to be able to benefit from the work."

"As the first SPORE to be awarded to the institution, this is a significant advance," said Dr. Stan Gerson, Asa and Patricia Shiverick- Jane Shiverick (Tripp) Professor of Hematological Oncology and director of the Case Comprehensive Cancer Center and the Seidman Cancer Center at University Hospitals Case Medical Center. "The grant validates our priority to develop strong, coordinated and integrated cross-disciplinary teams to investigate and treat complex cancers. This reflects our approach to all of the major cancers."

Main SPORE research studies include:

• Developing new drugs for preventing colon cancer.
• Developing new tests to identify individuals at risk of developing colon cancer.
• A clinical trial at the Seidman Cancer Center of a non-invasive stool DNA test for early detection of colon tumors.
• Developing new tests to distinguish colon cancers that can be cured by surgery alone from those that require further treatments such as chemotherapy and radiation.
• Identifying the causes of the increased death rate from colon cancer among African-American men and women, with the aim of developing better treatments for these cancers.
• Identifying genes that cause certain families to be vulnerable to cancer of the esophagus and/or the potentially precancerous disease known as Barrett's esophagus.

SPORE Researchers Include:

• Sanford Markowitz, MD, PhD, the Dr. Sanford Markowitz/Frances Wragg Ingalls Professor of Cancer Genetics at Case Western Reserve University School of Medicine and medical oncologist at University Hospitals Seidman Cancer Center, SPORE Director.
• Nathan Berger, MD, the Hanna-Payne Professor of Experimental Medicine and University Distinguished Professor at Case Western Reserve University School of Medicine, and hematologist-oncologist at University Hospitals Seidman Cancer Center, SPORE Co-director.
• Joseph E. Willis, MD, Associate Professor and Vice Chair, Department of Pathology, Case Western Reserve University School of Medicine and University Hospitals Case Medical Center.
• Li Li, MD, PhD, Associate Director for Prevention Research, Case Western Reserve University School of Medicine and University Hospitals Case Medical Center; Associate Professor of Family Medicine, Epidemiology and Biostatistics at Case Western Reserve University School of Medicine.
• Gregory Cooper, MD, Professor of Medicine, Oncology and Epidemiology and Biostatistics, Division of Gastroenterology, Case Western Reserve University School of Medicine and University Hospitals Case Medical Center.
• Zhenghe Wang, PhD, Assistant Professor of Genetics, Case Western Reserve University School of Medicine.
• Amitabh Chak, MD, Professor of Medicine, Case Western Reserve University School of Medicine and gastroenterologist at University Hospitals Case Medical Center.
• Robert Elston, PhD, Amasa B. Ford and University Distinguished Professor and Chair, Department of Epidemiology and Biostatistics, Case Western Reserve University School of Medicine.
• Martina Veigl, PhD, Associate Professor in the Division of General Medical Sciences, Biochemistry and Environmental Health Sciences, Case Comprehensive Cancer Center, Case Western Reserve University School of Medicine.
• Jill Barnholtz-Sloan, PhD, Associate Professor in the Division of General Medical Sciences and Epidemiology and Biostatistics, Case Comprehensive Cancer Center, Case Western Reserve University School of Medicine.
• Janet A. Houghton PhD, Chair, Department of Cancer Biology, Betsy B DeWindt Endowed Chair for Cancer Research, Lerner Research Institute Cleveland Clinic.
• John Goldblum, MD, Chair, Anatomic Pathology, Cleveland Clinic Professor of Pathology, Cleveland Clinic Lerner College of Medicine.
• Ian Lavery, MD, FACS, Digestive Disease Institute, Department of Colorectal Surgery, Cleveland Clinic.
• Neal J. Meropol, MD, Professor of Medicine, Chief, Division of Hematology and Oncology at Case Western Reserve University School of Medicine and University Hospitals Case Medical Center, Associate Director for Clinical Research, Case Comprehensive Cancer Center.
• James K. V. Willson, MD, Director of Simmons Cancer Center at the University of Texas Southwestern Medical Center.

Drs. Markowitz and James K. Willson discovered that the gene 15-PGDH naturally suppresses colon cancer and also regulates responses to tumor prevention with the drug Celecoxib. They lead the investigation into how individuals' natural levels of 15-PGDH expression may make them resistant or susceptible to tumor formation, identifying individuals at particularly high risk. They will examine whether differences in the gene are integral to tumor development in men versus women, and African-Americans versus Caucasians. The researchers will also seek to develop drugs that will increase 15-PGDH levels to provide a new class of agents for colon cancer treatment and prevention.

Drs. Gregory S. Cooper and Li Li are working on a non-invasive stool DNA test for early detection of colon tumors as a way to reach people who have not undergone or cannot afford a colonoscopy. They will begin a clinical trial conducted in both suburban and city neighborhoods, with the aim of raising screening rates for medically well-served and underserved parts of the community.

Drs. Joseph E. Willis and Sanford Markowitz were part of a team that sequenced what is called the colon cancer genome, which identified 140 genes that are targets of mutations in late stage cancer. Drs. Willis and Zhenghe Wang, Assistant Professor of Genetics, now lead an effort to identify the specific mutations that distinguish cancers that metastasize and those that do not. They will also seek to identify gene mutations associated with vulnerability according to race and gender. The findings will then be used to develop tests that would enable doctors to determine whether a patient requires surgery alone or requires chemotherapy and radiation following surgery.

Drs. Amitabh Chak and Robert C. Elston lead the esophageal cancer project. They will study a group of individuals from families in which multiple individuals have developed esophageal cancers and/or Barrett's esophagus. Using the newest generation of DNA sequencers, they will seek to identify the specific genes that cause certain individuals to become vulnerable to developing Barrett's esophagus and esophageal cancers.

Drs. Berger, Houghton and Meropol will coordinate the SPORE Pilot Project Program to develop new research initiatives in gastrointestinal cancer. They will also coordinate a SPORE Scholars Training Program to recruit, train and retain the most outstanding physicians and scientists to the region to engage in gastrointestinal cancer research and patient care.

A community advisory board will meet with SPORE researchers on a regular basis to advise on research directions and ensure dissemination of advances in the public interest.